It could be a jealous trainer who doesn't like the attention that girl - Ash is getting. This trainer might try to undermine her at every turn during Pokemon battles.
Maybe a scientist who originally caused Ash to turn into a girl, but now wants to use her for some unethical experiments related to the new form and Pokemon abilities. So he becomes the main antagonist as he constantly tries to capture girl - Ash.
There could be an organization that believes only male trainers should exist. They see girl - Ash as a threat to their ideology and try to stop her from continuing her Pokemon journey. They might spread false rumors about her or try to sabotage her attempts to enter Pokemon tournaments.
Maybe Team Rocket could be the main antagonist. They might see Ash's transformation as an opportunity to finally capture Pikachu. Since Ash is in a more vulnerable state as a girl, they could try to use different tactics to take advantage of the situation.
Maybe the main antagonist is an evil scientist. The scientist has been studying Pokémon transformations and when he sees Ash turn into Pikachu, he wants to experiment on him. He chases Ash around, trying to capture him with all kinds of high - tech devices. This forces Ash to use his Pikachu form's abilities and his human knowledge to outwit the scientist.
There could be a mad scientist - type character who created the situation where Ash turned into a Latias in the first place. But then, this character wants to keep Ash in that form to study him and use his new - found Pokemon abilities for their own gain. They would be the main obstacle for Ash in his journey to turn back into a human.
Team Rocket could be the main antagonists. They might see Ash's transformation into Mew as a way to capture a powerful Pokémon - like being. They could devise all sorts of plans to catch him, thinking that they can use Mew - Ash's powers for their own evil purposes.
Team Rocket could still be the main antagonists. They might see Ash as a Pikachu and try to capture him more than ever, thinking he's a special Pikachu. Maybe they believe he has some sort of new power because of his transformation.
It could be an evil wizard who was the one who actually caused Gumball to turn into a girl in the first place. The wizard has some ulterior motives, like using Gumball's new form to gain power or to cause chaos in the town. He tries to prevent Gumball from finding a way to turn back and keeps creating obstacles for Gumball and her friends.
It could be a villain who is obsessed with creating chaos through strange transformations. This villain might have targeted Deku specifically because of his status as a rising hero. They want to see how Deku will cope with being turned into a girl and use it to undermine his confidence and hero image.
Ganon could still be the main antagonist. Even though Link has turned into a girl, Ganon's goal of taking over Hyrule remains the same. He might underestimate Link in her new form, which could give Link an advantage. For example, Ganon might not expect the girl - Link to be as strong or resourceful as the male Link, but she proves him wrong.
Perhaps a jealous classmate who has always been in Izuku's shadow. Now that Izuku is a girl, this classmate sees an opportunity to undermine her. They spread rumors about how Izuku's transformation is some sort of cheat or that she's not the same reliable person she was as a boy. This classmate's actions and attempts to sabotage Izuku would make them the main antagonist.
There could be an ancient evil spirit that was released when Aang turned into a girl. This spirit feeds on chaos and the disruption of natural order. It sees Aang's transformation as a sign of the world being out of balance and tries to make it even worse. It might target Aang specifically because he is the Avatar and his new form gives it an opportunity to create more disorder.