What attackers do. Attackers use a protocol on a port where it does not normally run, such as web traffic on an unusual high port, to slip past simple filtering. This serves the Command and Control tactic.
How to defend. Restrict outbound traffic to the ports and protocols the business needs, and send web traffic through proxies. Use network monitoring that identifies protocols by content rather than port number. Correlate firewall logs with endpoint data so you can see which process opened each unusual connection. Review exceptions to egress rules regularly so temporary openings do not become permanent.
Signs to look for. Look for web or other common protocols on unusual ports, outbound connections to high ports from hosts that do not need them, and protocol mismatches flagged by network sensors. A common gap is permissive outbound rules that allow any port.