Strangers have always been a sticking point for the Hamatos, and Donatello is no exception. By the point he's at, though, he's gotten significantly better at dealing with strangers. When the family first met humans personally, Don's responses were fraught with anxiety and uncertainty; by now, though, he's comfortable enough that he at least makes attempts to welcome strangers with open arms. There are signs that a lot of his earlier discomfort comes from the constant awareness that his physical differences and isolated upbringing make him an Other: for instance, when they met Professor Honeycutt (an alien whose mind had accidentally ended up in a robotic drone), Donatello seemed comfortable with him essentially immediately, trading theories with him right off the bat - though perhaps having the professor willing to assist his family with escape was a big factor in his easy acceptance.
Still, there is evidence that Donatello's desire to understand and fix can bridge the gap between him and other people. One of the best examples of this is in the form of the genetically modified humans trapped in the Y'Lyntian underground city. Though these humans were strangers to him, Donatello was moved by their plight and resolved to rescue them. While his brothers accompanied him on the missions to Y'Lyntis, Donatello was the one who promised to save the humans trapped by needing the energy of the Crystal Moon; in the process, he made many friends, including a human named Sydney who had been one of the few remaining experiments that hadn't lost themselves entirely to their modifications.
Donatello may be a geek, but he's not completely lacking in social graces. While his brothers have done the majority of socializing for the family (with Michelangelo being the prominent one), Don tends to make the deeper intellectual connections. His most notable friendship is that of April O'Neil, a human woman and a computer scientist who the Turtles rescued from a robotic attack early in the series. Since then she's been a close friend of all of the Turtles, but Donatello has especially taken a liking to her quick wit and deep knowledge of mathematics. They're often collaborating together in episodes where they need the combined brainpower to get things done quickly. Donatello also talks to her of his own accord all the time (he's seen having an IM chat with her before Ultimate Drako shows up, for instance). He also has the closest relationship with a fellow mutant, the crocodile Leatherhead, who's also a scientist; it seems that Donatello gets along best with other intellectuals, as he has a more strained relationship with Casey Jones, the hotheaded vigilante friend of the Turtles. (He still clearly trusts Casey, though, and seems to appreciate him keeping Raphael from getting into too much trouble!)
Still, without his family to help smooth things over, Donatello is quicker to be defensive and mistrusting. Seeing Usagi Yojimbo trying to assist Leonardo while he was poisoned at the Battle Nexus got Don's hackles up. He had to be talked down from his defensiveness towards Usagi, though when the ronin proved himself trustworthy Don was willing to fight by his side. In absence of his family, Donatello might need more persuasion to come to trust people than he has in the past. Despite this, the unusual setting of Iniidae, and the knowledge that his family is safe elsewhere, should go some way towards easing the transition for Donatello.
Revision/Addition: Don and Strangers
Still, there is evidence that Donatello's desire to understand and fix can bridge the gap between him and other people. One of the best examples of this is in the form of the genetically modified humans trapped in the Y'Lyntian underground city. Though these humans were strangers to him, Donatello was moved by their plight and resolved to rescue them. While his brothers accompanied him on the missions to Y'Lyntis, Donatello was the one who promised to save the humans trapped by needing the energy of the Crystal Moon; in the process, he made many friends, including a human named Sydney who had been one of the few remaining experiments that hadn't lost themselves entirely to their modifications.
Donatello may be a geek, but he's not completely lacking in social graces. While his brothers have done the majority of socializing for the family (with Michelangelo being the prominent one), Don tends to make the deeper intellectual connections. His most notable friendship is that of April O'Neil, a human woman and a computer scientist who the Turtles rescued from a robotic attack early in the series. Since then she's been a close friend of all of the Turtles, but Donatello has especially taken a liking to her quick wit and deep knowledge of mathematics. They're often collaborating together in episodes where they need the combined brainpower to get things done quickly. Donatello also talks to her of his own accord all the time (he's seen having an IM chat with her before Ultimate Drako shows up, for instance). He also has the closest relationship with a fellow mutant, the crocodile Leatherhead, who's also a scientist; it seems that Donatello gets along best with other intellectuals, as he has a more strained relationship with Casey Jones, the hotheaded vigilante friend of the Turtles. (He still clearly trusts Casey, though, and seems to appreciate him keeping Raphael from getting into too much trouble!)
Still, without his family to help smooth things over, Donatello is quicker to be defensive and mistrusting. Seeing Usagi Yojimbo trying to assist Leonardo while he was poisoned at the Battle Nexus got Don's hackles up. He had to be talked down from his defensiveness towards Usagi, though when the ronin proved himself trustworthy Don was willing to fight by his side. In absence of his family, Donatello might need more persuasion to come to trust people than he has in the past. Despite this, the unusual setting of Iniidae, and the knowledge that his family is safe elsewhere, should go some way towards easing the transition for Donatello.