I think it's April's problem. Donnie made it clear that he likes her. If she liked him, she would have responded by getting into a relationship with him. However, she never kissed him in a romantic way. The fact that April never tells this to Donnie honestly, to me, seems to be because she doesn't want to hurt Donnie's feelings. Nevertheless, I think this deceives Donnie into thinking that there's maybe still a shot. I personally think she'd do him a favor by telling him honestly that she doesn't have feelings for him.
I think April holds prejudice against the turtles in that she doesn't believe the turtles are human, even though the turtles are mentally human. She believes that the turtles are somewhat responsible for her having to fight aliens rather than living like a normal girl. Because of this, I think there's no way she'd want to get romantic with Donnie.