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I feel like you're conflating the Joanne ending with the rest of her route and forgetting that the characters don't have the same insight into her situation that you now do.

It's easy to complete the Joanne ending and say "ah, so that's what she wants" and to look back over the rest of her route with that insight. But the characters in the game don't have that leisure. They don't know that she wants to become human; only that she keeps harming and denigrating herself. They don't link her self-harm with her not feeling comfortable in her own body; they only see self-destructive behavior.

Take the other ending, for instance. She isn't being confined because she wants to become someone else, or to stop her from undergoing such a transformation. She's confined because she's repeatedly self-harmed, and has now started physically hurting the people around her.

As for the Joanne ending, I understand your concerns with Sable's reaction, but I think it speaks more to his shock than anything. He hasn't seen her in months, now she's suddenly lost her demi-human aspects and taken on a new name. His inability to immediately adapt to her new name and appearance is unfortunate, but I don't see it as transphobic.

If that ending lasted a bit longer, then he might have gotten used to calling her by her new name. After having a chance to sit down and talk with her about her transformation, he might be able to accept that this is what she wants, and that what he called mutilation is actually something far more positive for her. Of course, the game ends before they have such a chance, so all we see is his initial failure to cope with this sudden change.

Anyway, if you view Sable's reaction in the Joanne ending as transphobic, then I can at least understand why. But I don't see how you can apply that to the rest of her route or the other endings. Their desire is to stop their self-harming friend, who's been overworking herself, not sleeping or eating properly, and violently attacked someone, from spiraling out of control any further.

I'm trying to inform my reading of the end where Joanne gets stuck in Amadronia by what I've seen in the other endings so conflating them is certainly a risk. When I saw the ending in which Joanne stays in Amadronia under Sable's guidance it reads quite well. Joanne appears to be suffering an analogue of trauma induced body dysmorphia. With the information he has it's perfectly reasonable for Sable to assume this is in her best interests, even if Amadronia is far from an ideal environment there really isn't a suitable facility for her or any of the demihumans still locked in the asylum. The problems only arise when we see what Sable does when he realises what he wants and what Joanne wants are in conflict.

The idea that Sable is shocked and reacts poorly tracks very well with his character. He's a shut-in with a slightly problematic fixation on demi-humans. If the story hadn't stopped there I'd probably assume he would eventually learn his lesson and apologise. Since it does cut there the place where it cuts has additional significance and since it's a bad end it seems we're to assume the current situation is extremely bad. The current situation is Joanne is genuinely happy for the first time we've seen her, she's comfortable, she's stopped self-harming. The implication is that this is bad because Sable believes she should be forced to live as her birth species and he specifically uses transphobic language to dismiss her. Since he's the one unhappy with the current situation and this is a bad end it feels like we're supposed to agree with Sable here. 

If that's a bad reading then the implications on the main ending are substantially different. Amadronia is still a terrible environment for Joanne, Sable is still hopelessly out of his depth. But if he is prepared to put her needs above his own after all then the ending is bittersweet rather than pure grimdark.

That sounds reasonable to me. I hope that the continuation of Jorou's route in SG2 sheds a better light on all of this. The Joanne ending is obviously too brief to cover the breadth of the issues involved here, and doesn't do either character the courtesy of a proper discussion. SG2 is still a long way off, but I'll keep this conversation in mind for when it does reach that stage of development.