@nebulon I have identified that it is an issue with multisite and the setting
define( 'DOMAIN_CURRENT_SITE', 'xxx.de' );in the wp-config file. This does not seem to be getting updated automatically and hence the change needs to be made manually (and also in the database).
Sorry, I didn't mention that it was a mutlisite installation before because I couldn't see any reason for that to affect the smtp plugin settings.