When to include the region, and when not to
A bare language subtag — en, de, ar — is correct and sufficient for most pages. Add a region only when it changes something real: en-GB against en-US affects spelling and date formats; pt-BR against pt-PT affects vocabulary and grammar substantially enough that readers notice.
Adding a region you do not mean is not harmless. en-US on a British site is a small factual error that hreflang and content signals then have to contradict.
Passages in another language take their own lang on the surrounding element — a quotation, a foreign-language term, a code sample — so a screen reader switches pronunciation for that run and switches back afterwards.