Update: the problem described in this article seems to be resolved in Fedora 36 (NetworkManager 1.38.0-2.fc36). It is still present in Fedora 35 (NetworkManager 1.32.12-2.fc35).

Update: there a companion article about solving this problem for Wireguard in here.

In an the Manage Linux client DNS settings in OpenVPN and Wireguard article we described how to use the update-systemd-resolved script to update systemd-resolved per-link DNS servers automatically based on DNS servers pushed from an OpenVPN server. This is very convenient if you have to be connected to multiple remote locations each with their own DNS servers and zones.