Perhaps an ancient dragon that has been sleeping for centuries and wakes up to find Astrid turning into a dragon. This dragon sees Astrid as an abomination because she was not born a dragon but is becoming one through some unnatural means. So, it decides to hunt her down and destroy her.
Perhaps a jealous wizard. He was once friends with Astrid but when he sees her gain the power and beauty of a dragon, he becomes envious. He starts to cast spells to make Astrid's life as a dragon difficult and tries to steal her new - found powers for himself.
It could be a dragon hunter who sees Hiccup in his dragon form and wants to capture him for study or to use his unique abilities for evil purposes.
One possible plot could be that Astrid is cursed by an evil sorcerer. At first, she has no idea what's happening to her but slowly starts to notice physical changes like her skin getting scaly. As she turns more and more into a dragon, she has to struggle to maintain her relationships with her friends who are initially afraid of her new form. Eventually, she discovers a way to break the curse through an ancient magic ritual.
In the fanfic, Astrid could be part of a scientific experiment gone wrong. The experiment was meant to study dragon DNA, but something malfunctioned and she starts to transform. She then embarks on a journey to find a cure. Along the way, she discovers that being a dragon gives her a unique perspective on the world and she has to decide if she really wants to go back to being fully human.
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.