Upon receiving the HTTP request from a podcast client, render a new version of the MP3 file with an up-to-date advert inserted. This version can be cached for a pre-specified period and then replaced later. You can't really get any tracking information to do dynamically targeted ads from the request, but for a podcast this doesn't matter much, as the hosts are typically aware enough of their listener demographic.

Dynamic Ad Insertion. The file server guesses your location/demographic based on the user agent and ip address and then splices ads into the mp3 as it is sent to you.