Most of the ones I get are generic mass mailshots (many even have loads of other addresses in the CC field LOL), I just mark them as spam and don’t worry any further. If however they have taken the time to send a personalised request that specifically references things to show they have put some effort in, I have no issue responding, sometimes that will be a polite thanks but no thanks, other times it may be drop in for a chat.
No, but off topic spam may be.