"What's up?" or here (West Midlands of England) commonly just "sup" is a general greeting, you can response with answers like "Not much", "Nothing", "Alright" etc. In this context, the response is just a return of the greeting, or a confirmation that all is going normally.

What does it mean when someone says what's up?

If you say to someone 'What's up? ' or if you tell them what's up, you are asking them or telling them what is wrong or what is worrying them. [informal]

What does it mean when a guy says what's up?

"What's up" can be an informal greeting as well as a way to ask what is going on, that is, what is happening, or what has been happening. It might itself be a reply to a request of some sort. For example, someone might call you on the phone and ask you to come and see them.