In my experience, what would happen would be:
A chunk of your readers who dig your writing and art style will probably follow you to the new comic. There are usually some die-hard fans who will read everything you make, even if the genre shifts hugely. If your fantasy work already had some LGBTQIA+ themes in it, you might even find a significant portion of your fans are really excited for a new work that more focuses on those themes!
A chunk of your readers won't follow you to the new comic. The further it is from the previous one, the more dropoff you should expect. The vast majority of them will be chill about it, like they don't dislike you, but your new thing just... isn't their thing. How many of us who love Fullmetal Alchemist have the same passion for Silver Spoon? (I actually like Silver Spoon, but a comic about a guy at agricultural college is VERY different from Arakawa's previous dark fantasy action-adventure). A lot of readers might try your new thing for a bit, but then drop off.
A very small minority of people will express annoyance or disappointment that your new content isn't more of the same. The bigger your following, the larger the number of people like this will likely be, because everyone has a percentage of fans like this, so it's kind of proportional to your following. 1% of a 100 person following is one person, but 1% of a 1 million person following is ten thousand people, so on the biggest webcomics, the outcry can seem overwhelmingly huge, even if there are hundreds of thousands of perfectly happy readers.
You'll pick up new fans for the new work. Some of them will have absolutely zero interest in your past work (Like Homestuck fans who have never read Problem Sleuth and have no interest in it because it doesn't have shippable teenage characters and that, more than the complexity and humour, was the main draw for them).
So yeah, you will lose some people, it's definitely worth being braced for it, but most creators recover from it and some even go on to greater success on switching genre.