Certainly a possibility, but I don’t really expect it to be a common concern. Defederation is mostly about keeping problematic people out when an instance’s admins either can’t or won’t resolve whatever problem is at play. Most instances will never even realize a single-user instance is lurking at all if they don’t bother to crawl the logs and said user doesn’t cause a scene.

I’d expect most whitelist-only instances will have been that way from the start instead of growing large and then shutting the door, because the goals of running an instance like that are fundamentally different.