Maybe the main antagonist is a secret organization within the hero society that doesn't want young heroes to grow up and change the status quo. Now that Deku is an adult, they try to eliminate him to prevent any potential changes he could bring to the hero world.
It could be an older version of a villain Deku has faced before. This villain has grown stronger over time and now that Deku is an adult, they see it as a chance for a rematch. They might also be jealous of Deku's rapid growth and new adult form.
A new villain could emerge who is specifically targeting adult heroes. Since Deku has now become an adult, he becomes a prime target. This villain might have a grudge against the hero society's adult leadership and see Deku as a symbol of that.
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.
It could be a new villain who has the power to manipulate memories. This villain might target Deku specifically because he sees Deku as a threat to his plans. He wants to erase Deku's memory so that he can't interfere with his evil schemes in the hero world.
A powerful and corrupt Pokemon trainer could be the antagonist. This trainer is jealous of the boy's unique transformation into a Pokemon. He wants to use the boy's powers for his own gain, like winning all the Pokemon battles and championships. So, he hunts the boy down, causing all sorts of trouble for him during his journey as a Pokemon.
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.
Perhaps a jealous trainer. This trainer has always been envious of Ash's success and now that Ash is in a vulnerable state as a Zorua, the trainer sees an opportunity to get rid of him for good. The trainer could try to use his own Pokémon to capture Ash or even harm him, making the trainer a formidable antagonist in the story.
Perhaps an evil mage who actually intended for the transformation to go wrong on purpose. They might want to use Sans' new female form to cause chaos in the Underground. They could be trying to manipulate Sans into doing bad things or using her to get to other important characters.
Maybe a powerful and envious Mewtwo could be the antagonist. Since Ash has now become a Mew, Mewtwo might feel threatened or think that Ash doesn't deserve such power. So, Mewtwo could try to fight Ash to prove his own superiority.
It could be a powerful vampire clan that doesn't want Harry, a new vampire, to disrupt their ways. They might try to either kill him or force him to join their ranks against his will. They could see him as an outsider who doesn't belong in the vampire world and a potential danger to their secrecy.
It could be a new villain who is specifically targeting Gohan because of his new form. This villain might see Gohan's transformation as a sign of weakness or an opportunity to mess with the Z - fighters. Maybe they want to use Gohan's confusion and the chaos it causes among his friends and family to their advantage.
It could be someone who wants to take advantage of Minato's new female form. Maybe a villain who has a vendetta against Minato in his original form and sees this as an opportunity to further humiliate or harm him.