Why did he change?

You would think so, but that would make for a completely different movie.

I try not to get too tied up with convenient plot devices. Especially in a film like this where everything else is damn near perfect.

AIRTIGHT LOGIC WOULD FAIRLY WELL KILL ENTERTAINMENT.

The explanation doesn't make sense. You just have to overlook that.

Still a great movie.

This is the main thing that doesn’t make any sense.

Remember when Seth injured himself in bed by getting that piece of metal stuck in his back? This is the beginning not only of his psychological change, but also of his physical change. Immediately afterwards he has a revelation about "the flesh" which leads to him transporting himself and the fly, merging their DNA.

As injuries heal, the body repairs the cells according to instructions in the DNA, but since Seth's DNA has now been merged with the fly's, his body is creating cells based on those merged instructions. This is why the first signs of Seth's transformation take the form of insect hairs growing out of the wound on his back. In essence, this injury, and the body's natural response to repair it, became the catalyst for a genetic transformation that eventually took over his entire body.

This process is much like William Birkin's transformation into the G-Monster in Resident Evil 2. Birkin receives critical gunshot wounds to his arm and chest before injecting himself with the G-Virus, which not only repairs these injuries, but also replaces the injured cells with those of the monster. This is why Birkin has a large mutated claw for an arm and an eyeball growing out of his chest in his first form. With each encounter you have with him in the game, you injure him even more, and as his injuries heal, the transformation becomes more complete to the point where he devolves from a biped to a quadruped, and finally to a massive blob of teeth and tentacles. In effect, the protagonist's attempts to defeat it served only to trigger the next stage in its mutation.

He began mutating as soon as he got out the telepod, but the process took days or weeks. The telepod spliced their genes togetherl, so it slowly started breaking down and rebuilding his anatomy at the molecular level. Like a wax figurine under a heat lamp, it appears stable but soon the underlying foundation gives way.

I'm afraid we have to chalk this one up to bad writing.
Simply because, at the end, the same procedure brings immediate results fusing fly and teleporter.

But if that was not the case, I would tell you that the combined dna starts changing his body like cancer or some other dna mutation, so it is progressive, not immediate.

He mutates and not the fly because there's way more Brundle than fly.

It actually makes sense. In order for a human to become a human-fly hybrid, he needs both human-fly DNA and also needs time for that DNA to grow.

The telepod transformed his human DNA into human-fly DNA instantly, but the telepod does not simulate growth. He had to do that on his own.

Obviously changing your DNA like that would kill you instantly but you would die looking like a human. The reason a telepod wouldn't simulate growth is because it has no way to know what a fully grown human-fly would look like.

Where the movie gets it wrong is when it says he didn't absorb the fly, and instead spliced with its DNA. It should've said that both things happened, but that we couldn't see the absorption of the fly because of the size difference. We could see him absorb the telepod door because it was a much larger object.