I do not own Ponyo
Most of this is pure speculation on my part, like the negative effects of magic on the body and the true nature of Ponyo's sisters. Though, honestly, it makes a lot more sense to me that Ponyo's sisters are made of magic, especially since she kept changing them during the "wave running" scenes.
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Ponyo looks so happy, frolicking along side the human boy that she has promised to heart to.
The crystal ball provides a clear picture of his daughter's happiness, the bright cheeks and bubbling laughter are testimony to her joy.
It makes Fujimoto feel vaguely ill.
It isn't just that he is an overprotective father, that he admits to readily, but that his little girl is going to die.
She isn't immortal anymore, the magic that would have granted her eternal life no longer flows in her veins. Unlike him and her sisters, his beautiful, headstrong, temperamental daughter is truly mortal and living on borrowed time.
One fear is that she will regret giving up her magic. A child does not understand love as an adult or even a teenager does. Perhaps when she grows older, she will realize that she doesn't love Sosuke, or worse, that Sosuke does not love her. While he does admit that love is a brand of magic all it's own, it cannot compare to the feelings of rightness that true magic brings.
Another fear is that she will miss her siblings. It's only been a few months since Ponyo has become human, so she hasn't been homesick yet. But if she does want to see her sisters, she won't be able too. Without the magic that was her birthright, her sisters will seem to be normal fish to her, she won't understand them. Or, Fujimoto privately hopes this is not the case, she won't even be able to see them.
Her sisters are nothing more than semi-stable figments of Granmammare's love and his own magic. Ponyo is the only true flesh-and-blood child that they have managed to conceive. As their only true child, she is precious to him beyond all belief.
But, he bitterly thinks to himself, not precious enough for him to save her life.
Fujimoto's greatest fear though, is that Ponyo won't live long enough to experience true love. Transforming into a human is extremely taxing on living cells, more so since she used raw power to forcibly "evolve" herself into a girl. The sheer magnitude of power that she threw around before being mode-locked worries him greatly. He knows, from his own experience, that throwing out spells without proper limits results in horrifying backlash. And Ponyo never learned the proper spells to achieve the effects that she created.
The best case scenario is that there was no damage to her body and she'll live a long happy life. She and Sosuke will get married and have several children, and he'll end up being a grouchy old grandfather.
The sea wizard knows that there is no chance in Hell or Heaven that will happen. If there had been no damage, Granmammare would have never have let their daughter go so easily on such a flimsy pretense.
The worst case scenario, which he knows is almost inevitable, is that his fiery daughter will only live for a few years before her body destroys itself and she dies in pain. She might not even recognize that she is in pain during her last few months, if her brain is the first thing to deteriorate. And it most likely will be, especially since her brain was still developing when she met the boy.
A sharp stinging sensation forces him to unclench his hands, nails having gouged deep crescents into his flesh. Fujimoto looks away from the seeing crystal, the bright red of his blood stark against his unhealthily pale skin. Bile rises in his throat, as his mind suddenly imposes the image of his daughter's hand over his own. It's all too easy to imagine the red fluid as clotted lung blood, a result of failing lungs and dying cells.
Gritting his teeth, the wizard turns off the viewer, bitterly cursing himself for not preventing the entire incident. He should have known that she would sneak out and explore, he had done the same at her age. But he had been too obsessed with his grand plan, his ego blinding him to the needs and desires that his little girl had.
It's all his fault and he knows it.