What do we know? At least in h. sapiens it does. — 180 Proof
Science has no idea how brains produce consciousness. You would think, after all this time, we would have
some idea, but the theories are all over the place. Eventually, people are going to question basic assumptions, such as "matter is real" and "brains cause consciousness".
To tie this back to the OP, if there's no explanation for how our own brains make us conscious, why should we even consider the idea that consciousness can come from an entirely different substrate? Why is that even taken seriously? Aren't we getting ahead of ourselves?
"For starters, what difference would such a "possibility" make to us ontologically, existentially or pragmatically?"
If you knew for certain you were in a simulation, wouldn't you want to try and get in touch with the simulation creator?