How did American Indians react to American settlers in the late 1700s and early 1800s?

Most American Indians lived west of the Appalachians, so settlement had little effect on them.

Settlement affected American Indians very little, but they resented the arrival of explorers.

The two groups were trading partners, so both sides lived in peaceful coexistence.

American settlers and American Indians often clashed as settlement spread across the West during that era.

The best answer is D.

A is partly right but mostly wrong. It is in fact true that more American Indians lived west of the Appalachians than east of them at the time, but the answer is wrong because even those groups who lived to the west were still affected by settlement, since European diseases and the huge economic and cultural consequences of trade and displacement spread westward on trade routes even if Europeans themselves didn't.

B is wrong because settlement affected Natives in enormous ways; imagine if like a hundred people with chickenpox moved into your living room.

C is partly true; many Natives and many settlers were trading partners, but Natives and settlers hardly lived in "peaceful harmony."

That leaves you with D.

The answer to your question is "D".